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Abstract
The (seco) iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form two large families of plant-derived bioactive compounds with a wide spectrum of high-value pharmacological and insect-repellent activities. Vinblastine and vincristine, MIAs used as anticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to high market prices and poor availability. Their biotechnological production is hampered by the fragmentary knowledge of their biosynthesis. Here we report the discovery of the last four missing steps of the (seco) iridoid biosynthesis pathway. Expression of the eight genes encoding this pathway, together with two genes boosting precursor formation and two downstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologous production of the complex MIA strictosidine. This confirms the functionality of all enzymes of the pathway and highlights their utility for synthetic biology programmes towards a sustainable biotechnological production of valuable (seco) iridoids and alkaloids with pharmaceutical and agricultural applications.
Keywords
EXPRESSION, STATISTICAL-MODEL, PLANTS, PROTEINS, SYNTHASE, ENZYME, CYTOCHROME-P450, RAUWOLFIA-SERPENTINA, INDOLE ALKALOID BIOSYNTHESIS, SUBCELLULAR ORGANIZATION

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MLA
Miettinen, Karel, Lemeng Dong, Nicolas Navrot, et al. “The Seco-iridoid Pathway from Catharanthus Roseus.” NATURE COMMUNICATIONS 5 (2014): n. pag. Print.
APA
Miettinen, K., Dong, L., Navrot, N., Schneider, T., Burlat, V., Pollier, J., Woittiez, L., et al. (2014). The seco-iridoid pathway from Catharanthus roseus. NATURE COMMUNICATIONS, 5.
Chicago author-date
Miettinen, Karel, Lemeng Dong, Nicolas Navrot, Thomas Schneider, Vincent Burlat, Jacob Pollier, Lotte Woittiez, et al. 2014. “The Seco-iridoid Pathway from Catharanthus Roseus.” Nature Communications 5.
Chicago author-date (all authors)
Miettinen, Karel, Lemeng Dong, Nicolas Navrot, Thomas Schneider, Vincent Burlat, Jacob Pollier, Lotte Woittiez, Sander van der Krol, Raphael Lugan, Tina Ilc, Robert Verpoorte, Kirsi-Marja Oksman-Caldentey, Enrico Martinoia, Harro Bouwmeester, Alain Goossens, Johan Memelink, and Daniele Werck-Reichhart. 2014. “The Seco-iridoid Pathway from Catharanthus Roseus.” Nature Communications 5.
Vancouver
1.
Miettinen K, Dong L, Navrot N, Schneider T, Burlat V, Pollier J, et al. The seco-iridoid pathway from Catharanthus roseus. NATURE COMMUNICATIONS. 2014;5.
IEEE
[1]
K. Miettinen et al., “The seco-iridoid pathway from Catharanthus roseus,” NATURE COMMUNICATIONS, vol. 5, 2014.
@article{4420051,
  abstract     = {{The (seco) iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form two large families of plant-derived bioactive compounds with a wide spectrum of high-value pharmacological and insect-repellent activities. Vinblastine and vincristine, MIAs used as anticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to high market prices and poor availability. Their biotechnological production is hampered by the fragmentary knowledge of their biosynthesis. Here we report the discovery of the last four missing steps of the (seco) iridoid biosynthesis pathway. Expression of the eight genes encoding this pathway, together with two genes boosting precursor formation and two downstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologous production of the complex MIA strictosidine. This confirms the functionality of all enzymes of the pathway and highlights their utility for synthetic biology programmes towards a sustainable biotechnological production of valuable (seco) iridoids and alkaloids with pharmaceutical and agricultural applications.}},
  articleno    = {{3606}},
  author       = {{Miettinen, Karel and Dong, Lemeng and Navrot, Nicolas and Schneider, Thomas and Burlat, Vincent and Pollier, Jacob and Woittiez, Lotte and van der Krol, Sander and Lugan, Raphael and Ilc, Tina and Verpoorte, Robert and Oksman-Caldentey, Kirsi-Marja and Martinoia, Enrico and Bouwmeester, Harro and Goossens, Alain and Memelink, Johan and Werck-Reichhart, Daniele}},
  issn         = {{2041-1723}},
  journal      = {{NATURE COMMUNICATIONS}},
  keywords     = {{EXPRESSION,STATISTICAL-MODEL,PLANTS,PROTEINS,SYNTHASE,ENZYME,CYTOCHROME-P450,RAUWOLFIA-SERPENTINA,INDOLE ALKALOID BIOSYNTHESIS,SUBCELLULAR ORGANIZATION}},
  language     = {{eng}},
  pages        = {{11}},
  title        = {{The seco-iridoid pathway from Catharanthus roseus}},
  url          = {{http://dx.doi.org/10.1038/ncomms4606}},
  volume       = {{5}},
  year         = {{2014}},
}

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